1. Field of the Invention
The present invention relates to extracts of ginkgo biloba leaves with reduced 4'-O-methyl pyridoxine and biflavones content, a process for their preparation and medicaments comprising said extracts, which do not exhibit undesirable side effects initiated by 4'-O-methyl pyridoxine and biflavones even at high dosages.
2. Present State of the Art
Extracts of Ginkgo biloba leaves have been used therapeutically for 30 years. The Commitee E of the Federal Health Office (Bundesgesundheitsamt) in Berlin has acknowledged that medicaments comprising defined extracts are effective in the symptomatic treatment of performance disturbances caused by cerebral insufficiency, peripheral occlusive disease, vertigo and tinnitus (BAnz No. 133, Jul. 19, 1994). These extracts are characterized by a content of 22 to 27% flavone glycosides, 5 to 7% terpene lactones, 2.8 to 3.4% thereof being ginkgolides A, B and C, and 2.6 to 3.2% bilobalide, and by a maximum content of 5 ppm ginkgolic acids (alkyl phenol compounds). Such extracts of Ginkgo biloba leaves and methods for their preparation are known from DE 39 40 091 (EP-B-0 431 535) and DE 39 40 092 (EP-30 B-0 431 536).
The occurence of 4'-methoxy pyridoxine (4'-O-methyl pyridoxine) in ginkgo biloba seeds has been described by Wada et al., Chem. Pharm. Bull. 33 (1985), 3555-3557. This compound causes symptoms of poisoning like convulsions and unconsciousness ("Gin-nan food poisoning" and "Gin-nan sitotoxism"), which may occur after consumption of larger amounts of ginkgo seeds. Therefore, the discoverer of this compound named it "ginkgotoxin". In a later work the same research group found out that 4'-O-methyl pyridoxine is absent in ginkgo leaves (Wada et al., Biol. Pharm. Bull. 16 (1993), 210-212). Contrary to this statement is a recently issued publication reporting on the isolation and identification of 4'-O-methyl pyridoxine from ginkgo leaves (Arenz et al., Planta Medica 62 (1996), 548-551). In this work commercial preparations with extracts of ginkgo biloba leaves have been analyzed with respect to their anti-vitamin B.sub.6 (4'-O-methyl pyridoxine) content and concentrations of between about 4 and 10 .mu.g/ml of liquid medicinal form have been found. This corresponds to a concentration of about 100 to 250 ppm in the dry extracts processed to preparations.